Catalytic asymmetric synthesis of α-methyl-p-boronophenylalanine. Issue 10 (1st June 2018)

• Record Type: Journal Article
• Authors: Harada, Shingo; Kajihara, Ryota; Muramoto, Risa; Jutabha, Promsuk; Anzai, Naohiko; Nemoto, Tetsuhiro
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 10(2018)
• Page Start: 1915
• Page End: 1918
• Publication Date: 2018-06-01
• Subjects: BNCT -- BPA -- Drug delivery -- Phase transfer catalysis -- Miyaura borylation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.03.075
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: We designed a novel candidate molecule for BNCT. ( S )-2-Amino-3-(4-boronophenyl)-2-methylpropanoic acid was synthesized. Phase-transfer catalyzed asymmetric alkylation was utilized as a key step. A Miyaura borylation reaction enabled the introduction of a boron functionality. Abstract: p -Boronophenylalanine (l -BPA) is applied in clinical settings as a boron carrier for boron neutron capture therapy (BNCT) to cure malignant melanomas. Structural modification or derivatization of l -BPA, however, to improve its uptake efficiency into tumor cells has scarcely been investigated. We successfully synthesized ( S )-2-amino-3-(4-boronophenyl)-2-methylpropanoic acid in enantioenriched form as a novel candidate molecule for BNCT. Key steps to enhance the efficiency of this synthesis were enantioselective alkylation of N -protected alanine tert -butyl ester with a Maruoka catalyst and Miyaura borylation reaction to install the boron functionality.